ACTN4 and cancer: In the nucleus, actinin-4 is known to function as a co-activator of several transcriptional factors, independently from its cytoplasmic actin-binding function.32,33 Khurana et al. showed that overexpression of ACTN4 activated ERα-mediated transcription activity, whereas knockdown of ACTN4 inhibited oestrogen-mediated cancer cell proliferation.34 ER signalling may be activated in patients with ACTN4 CNI and promote the aggressiveness of HR-positive tumours.